Program Director/Principal Investigator (Last, First, Middle): Sivaramakrishnan, Shobhana ABSTRACT The long-term goal of this work is to improve understanding of the neural mechanisms that underlie hearing. To determine how acoustic information is processed by the brain, it is critical to elucidate how sound frequency is represented at different sound levels. This project focusses on the central nucleus of the inferior colliculus (ICC), the auditory nucleus in the midbrain that is critically important in regulating hierarchical processing of acoustic information between the ear and the auditory cortex. For its role in hearing, the ICC receives ascending inputs from most parts of the brainstem and is influenced by descending projections from the auditory cortex. In addition, it contains complex local circuits and unique cell types. Recent work demonstrates that local feedback circuitry in the ICC creates acoustically relevant codes despite inadequate brainstem input. This project aims to understand the mechanisms by which the ICC codes the frequency content of simple and complex sounds. Experiments are based on the broad hypothesis that the representation of frequency by the ICC depends on the spatio-temporal characteristics of its local circuits. Aim 1 will identify structure-function correlates of local circuitry and examine connectivity within and across frequency laminae. We will use electrophysiological recordings and optical imaging in brain slices to identify the mechanisms by which the two principal cell types in the ICC, disc-shaped and stellate cells, interact to generate a map of frequencies. Aim 2 will identify how local circuits contribute to frequency representation of simple sounds. In vivo electrophysiological recordings from the ICC of awake mice will be used to examine the contribution of local circuitry and voltage-gated ion channels to the receptive fields of ICC neurons. Aim 3 will identify how local circuits contribute to frequency representation of vocalizations, which are complex natural sounds. In vivo electrophysiological recordings from awake mice will be used to examine the cellular basis for an overrepresentation of high frequencies in the ICC, and the selectivity of neurons to vocalizations with different frequency content. Dysfunction of the ICC plays a critical role in hearing abnormalities. By examining how the arrangement of local circuitry in the ICC contributes to its importance in transforming frequency information from lower auditory nuclei, our work will lay the groundwork for the mechanisms that underlie the frequency re-organization in the ICC that accompanies auditory pathology and will identify the components of hearing disorders that originate in the lower brainstem, midbrain, or higher regions of the auditory hierarchy. 1